A conserved human T cell population targets mycobacterial antigens presented by CD1b

Nat Immunol. 2013 Jul;14(7):706-13. doi: 10.1038/ni.2630. Epub 2013 Jun 2.


Human T cell antigen receptors (TCRs) pair in millions of combinations to create complex and unique T cell repertoires for each person. Through the use of tetramers to analyze TCRs reactive to the antigen-presenting molecule CD1b, we detected T cells with highly stereotyped TCR α-chains present among genetically unrelated patients with tuberculosis. The germline-encoded, mycolyl lipid-reactive (GEM) TCRs had an α-chain bearing the variable (V) region TRAV1-2 rearranged to the joining (J) region TRAJ9 with few nontemplated (N)-region additions. Analysis of TCRs by high-throughput sequencing, binding and crystallography showed linkage of TCRα sequence motifs to high-affinity recognition of antigen. Thus, the CD1-reactive TCR repertoire is composed of at least two compartments: high-affinity GEM TCRs, and more-diverse TCRs with low affinity for CD1b-lipid complexes. We found high interdonor conservation of TCRs that probably resulted from selection by a nonpolymorphic antigen-presenting molecule and an immunodominant antigen.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD1 / immunology*
  • Base Sequence
  • Clone Cells
  • Crystallography, X-Ray
  • Flow Cytometry
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mycobacterium / immunology*
  • Mycobacterium Infections / immunology*
  • Mycobacterium Infections / microbiology
  • RNA / chemistry
  • RNA / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*


  • Antigens, CD1
  • Receptors, Antigen, T-Cell, alpha-beta
  • RNA

Associated data

  • GENBANK/JQ778257
  • GENBANK/JQ778258
  • GENBANK/JQ778259
  • GENBANK/JQ778260
  • GENBANK/JQ778261
  • GENBANK/JQ778262
  • GENBANK/JQ778263
  • GENBANK/JQ778264
  • PDB/4G8E
  • PDB/4G8F